7018-75-9Relevant academic research and scientific papers
Discovery and labeling of high-affinity 3,4-diarylpyrazolines as candidate radioligands for in vivo imaging of cannabinoid subtype-1 (CB1) receptors
Donohue, Sean R.,Pike, Victor W.,Finnema, Sjoerd J.,Truong, Phong,Andersson, Jan,Gulyás, Balázs,Halldin, Christer
, p. 5608 - 5616 (2008)
Imaging of cannabinoid subtype-1 (CB1) receptors in vivo with positron emission tomography (PET) is likely to be important for understanding their role in neuropsychiatric disorders and for drug development. Radioligands for imaging with PET are required for this purpose. We synthesized new ligands from a 3,4-diarylpyrazoline platform of which (-)-12a ((-)-3-(4-chlorophenyl)- N′-[(4-cyanophenyl)sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1- carboxamidine) was found to have high-affinity and selectivity for binding to CBi receptors. (-)-12a and its lower affinity enantiomer ((+)-12a) were labeled with carbon-11 (t1/2 = 20.4 min) using [11C]cyanide ion as labeling agent and evaluated as PET radioligands in cynomolgus monkeys. After injection of [11C](-)-12a, there was high uptake and retention of radioactivity across brain according to the rank order of CB1 receptor densities. The distomer, [11C](+)-12a, failed to give a sustained CB1 receptor-specific distribution. Polar radiometabolites of [11C](-)-12a appeared moderately slowly in plasma. Radioligand [11C](-)-12a is promising for the study of brain CB1 receptors and merits further investigation in human subjects.
Design, Synthesis, and Biological Evaluation of Novel, Non-Brain-Penetrant, Hybrid Cannabinoid CB1R Inverse Agonist/Inducible Nitric Oxide Synthase (iNOS) Inhibitors for the Treatment of Liver Fibrosis
Iyer, Malliga R.,Cinar, Resat,Katz, Alexis,Gao, Michael,Erdelyi, Katalin,Jourdan, Tony,Coffey, Nathan J.,Pacher, Pal,Kunos, George
, p. 1126 - 1141 (2017/02/19)
We report the design, synthesis, and structure-activity relationships of novel dual-target compounds with antagonist/inverse agonist activity at cannabinoid receptor type 1 (CB1R) and inhibitory effect on inducible nitric oxide synthase (iNOS). A series of 3,4-diarylpyrazolinecarboximidamides were synthesized and evaluated in CB1 receptor (CB1R) binding assays and iNOS activity assays. The novel compounds, designed to have limited brain penetrance, elicited potent in vitro CB1R antagonist activities and iNOS inhibitory activities. Some key compounds displayed high CB1R binding affinities. Compound 7 demonstrated potent in vivo pharmacological activities such as reduction of food intake mediated by the antagonism of the CB1Rs and antifibrotic effect in the animal models of fibrosis mediated by iNOS inhibition and CB1R antagonism.
Rapid and straightforward transesterification of sulfonyl carbamates
Isaksson, Rebecka,Kumpi?a, Ilze,Larhed, Mats,Wannberg, Johan
supporting information, p. 1476 - 1478 (2016/03/12)
A fast and convenient method for the alkoxy exchange of sulfonyl carbamates by simply heating in a chosen alkyl alcohol is described. No catalysts or additives are required. Microwave heating at 100-120 °C for 20-60 min resulted in good to excellent yields (53-93%) of alkyl (arylsulfonyl)carbamates where the alkyl part originates from the alcohol solvent. The developed protocol was applied to the synthesis of an angiotensin II type 2 receptor (AT2R) ligand.
